The haematological system and skin - Coagulation and the bone marrow in health and disease Flashcards
Thrombophilias - who should be screened
Patients with thrombosis who are young
Positive family history
Thrombosis in an unusual site
Recurrence
Females with recurrent foetal loss
Inherited thrombophilias
Factor V Leiden
Protein C deficiency
Protein S deficiency
Antithrombin III deficiency
Prothrombin mutation
Acquired thrombophilia
Oestrogen therapy, contraceptive pill
Malignancy
Pregnancy and puerperium
Lupus anticoagulant (antiphospholipid) syndrome
Raised plasma homocysteine (may also be inherited)
Lupus anticoagulant (antiphospholipid) syndrome - clinical features
CLOT
Clots: arterial/venous thrombosis
Lived reticularis
Obstretic loss: recurrent miscarriages
Thrombocytopenia
Lupus anticoagulant (antiphospholipid) syndrome - laboratory features
Prolonged APTT
Lupus anticoagulant (antiphospholipid) syndrome - Management
Lifelong anticoagulation
Management of warfarin - major bleeding
Stop warfarin
Administer IV vitamin K
Administer prothrombin complex ( or fresh frozen plasma if prothrombin complex unavailable)
Management of warfarin - minor bleeding
Stop anticoagulants
Administer IV vitamin K
Repeat INR after 24 hours, may need further vitamin K
Management of warfarin - no bleeding with INR > 8
Stop anticoagulants
Administer IV or oral vitamin K
Repeat INR after 24 hours
Management of warfarin - no bleeding with INR between 5-8
Withhold 1-2 doses of warfarin and restart at reduced dose
Review maintenance dose of warfarin
Heparin - management of over anticoagulation/bleeding
Stop heparin – short half-life, may be sufficient
Local measures e.g., apply pressure
Consider tranexamic acid
If bleeding, consider protamine sulphate
Look for cause e.g., incorrect dose, new renal failure
Before restarting check risk: benefit ratio
DOAC - management of anticoagulation/bleeding
- Stop DOAC
- Local measures e.g., apply pressure
- Consider tranexamic acid
Idracruzimab reveral agent for dabigatran
- Antidote to Xa inhibitors not yet available. In the meantime, in life threatening bleeding consider prothrombin complex concentrate
- Look for cause
- Before restarting check risk:benefit ration
Warfarin: risk factors for bleeding
- Elderly
- Renal failure
- Liver failure
- Recurrent falls
- Platelet of NSAIDs use
- Alcoholism
- Cancer
Leucocytosis - causes
Primary
- Leukaemia/ lymphoma/ myeloproliferative disorders
Secondary
- infection
- Inflammation
- Infarction
- Tumour
Thrombocytosis - causes
Primary - essential thrombocythemia
Secondary
- Infection
- Inflammation
- Infarction
- Tumour
Essential thrombocythemia - aetiology and pathophysiology
JAK2 mutation in 50% cases
Essential thrombocythemia - clinical features
Asymptomatic - at least 30%
Thrombosis (arterial/venous)
Headaches, visual disturbances
Excessive haemorrhage may occur spontaneously or after trauma or surgery
Pruritis and sweating are uncommon
Gout (raises uric acid)
Essential thrombocythemia - laboratory features
Raised platelet count
Raised red cell and/or white cell in 30%
Blood film - platelet anisocytosis with circulating megakarocyte fragments. Auto infraction of the spleen may case target cells, Howell-Jolly bodies
JAK2 mutation
Raised serum uric acid
Serum LDH normal
Bone marrow - hyper cellular + increased megakarocytes
Essential thrombocythemia - management
Aspirin only in younger patients < 40 years
Chemotherapy with hydroxycarbamide + aspirin in > 40 years
Alpha interferon (may be used in younger patients but needs injections and has side- effects - flu like symptoms)
Allopurinol for gout
True erythrocytosis “polycythaemia” - definition and causes
Definition
- Increased number of red cells
Causes
- Primary: Polycythaemia rubra vera
- Secondary: low oxygen e.g., cold, tumours, doping, high affinity haemoglobin
Apparent erythrocytosis - defenition and causes
Definition
- Reduced plasma volume
Causes
- Smoking
- Overweight
- Alcohol excess
- Medications e.g., diuretics
Polycythaemia rubra vera - aetiology and pathophysiology
Mutations of JAK2 in > 995% cases
Polycythaemia rubra vera - clinical features
- Aquagenic pruritus (itchiness after hot bath especially)
- ‘Ruddy complexion’/plethora/redness
- Teaches and visual disturbances
- Thrombosis (arterial/venous)
- Haemorrhage especially GI
- Splenomegaly
- Hyperviscosity symptoms: chest pain, myalgia, weakness, headache, blurred vision, loss of concentration
Polycythaemia rubra vera - Laboratory features
- Raised hb, haemoatocrit and red cell count
- Raised white cells and/or platelets (in 75% people)
- JAK2 mutation
- Raised serum uric acid
- Serum LDH normal or slightly raised
- Low serum EPO (to prevent further erythrocytosis)
- Hypercellular bone marrow with deplete iron stores
Polycythaemia rubra vera - management
Venesection +/- chemotherapy with oral hydroxycarbamide + aspirin
Plasmapheresis for hyperviscosity syndrome
PPI for patients with indigestion or history of GI bleeding
Allopurinol to prevent hyperuricemia
Polycythaemia rubra vera - prognosis
Development of myelofibrosis (in up to 30%
AML (in ups o 5%, not increased by hyrdoxycarbamide)
Thrombocytopenia - causes
Underproduction
- Drugs affect stem cell
- Liver failure
- Part of pancytopenia due to marrow failure
Peripheral destruction
- Autoimmune (ITP)
- Hypersplenism
- Drugs
- Infection/inflammation/ sepsis
Low blood counts caused by reduced production - causes
Myeloma
Myelodysplasia
Metastatic malignancy
Myelofibrosis
Leukaemia
Lymphoma
Aplastic anaemia
Haematinic deficiency
Immune thrombocytopenia purpura (ITP) - definition
Autoimmune disease of Unkown cause where the number of platelets is reduced
Immune thrombocytopenia purpura (ITP) - clinical features
Isolated thrombocytopenia:
- On incidental finding or
- Features of purpura or
- Other minor bleeding
Immune thrombocytopenia purpura (ITP) - management
Oral prednisolone - patients with a platelet of <30 × 10^9/L or a platelet count >30 × 10^9/L and features of minor bleeding/high risk
Splenectomy - refractory cases
Avoid platelet transfusions in the absence of life-threatening bleeding
Myelodysplasia (myelodysplastic syndrome) - definition
Haematopoietic stem cell malignancy where there is abnormal maturation as well as proliferation of cells in bone marrow.
It is characterised by peripheral blood cytopenia
Myelodysplasia (myelodysplastic syndrome) - Aetiology and pathogenesis
May be primary or secondary, as. consequence of a previous chemotherapy/radiotherapy
Myelodysplasia (myelodysplastic syndrome) - laboratory findings
Macrocytic anaemia
Pancytopenia
Blood film - Active, cellular marrow
Myelodysplasia (myelodysplastic syndrome) - differential diagnosis
Other causes of anaemia must be excluded
Myelofibrosis
Aplastic anaemia
Myelodysplasia (myelodysplastic syndrome) - management
Supportive care with red cell or platelet transfusion and antimicrobials may be required
Erythropoietin
Iron chelation theory to prevent iron overload
Chemotherapy
Allogenic stem cell transplant (may cure younger patients)
Aplastic anaemia - definition
Chronic pancytopenia associated with hypoplastic bone marrow
Aplastic anaemia - aetiology and pathogenesis
May be acquired or congenital (e.g., Fanconi’s anaemia), dyskeratosis congenital
Aplastic anaemia - epidemiology
May occur at any age, in either sex
Aplastic anaemia - Clinical features
Onset rapid (over few days) or slow (over weeks or months
Liver, spleen and lymph nodes not enlarged
Fanconi’s anaemia - genetic inheritance
Autosomal recessive
Fanconi’s anaemia - clinical features
- Presents in childhood
- Pigmentation abnormalities
- Hearing defects
- Renal abnormalities
- Genital abnormalities
- Solid tumours
- Short stature
Aplastic anaemia - laboratory findings
Normocytic anaemia or mild microcytic with a low reticulocyte
Pancytopenia
Blood film- hypo plastic with > 75% fat spaces (“empty” bone marrow)
Aplastic anaemia - management
Immunosuppression
Androgens
Stem cell transplantation is a cure in severe cases
Haemopoietic growth factors, granulocyte colony-stimulating factor may raise neutrophil count temproily
Blood product support
Myelofibrosis - aetiology and pathophysiology
Malignant proliferation of reticulin fibres in bone marrow causing anemia,
Myelofibrosis - epidemiology
Sexes affected equally
> 50 years
Myelofibrosis - clinical features
Frequent - fever, weight loss, pruritus, hepatomegaly and night sweats
Less common - gout, bone and joint pain
Late stages - abdominal swelling, ascites and bleeding from oesophageal varicose occur
Myelofibrosis - laboratory features
Normochromic normocytic anaemia
Leucocytosis and thrombocytosis occur early, and later leucopenia and thrombocytopenia
Blood film: red cell poikilocytes with teardrop forms
JAK2 mutation in 50% cases
LDH raise (unliked in PRV and ET)
LFTs are often abnormal because of extramedullary haemopoiesis
“Dry tap” on attempt of bone marrow aspiration
Myelofibrosis - management
- Chemotherapy with hydroxycarbamide
- JAK2 inhibitors
- Thalidomide - improves marrow function and reduces spleen size
- Supportive therapy with red cell transfusions, folic acid and occasionally platelett transfuion
- Iron chelation to prevent iron overload
- Splenectomy or splenic irradiation
- Allogenic stem cell transplantation: a cure for younger patients
Myelofibrosis - prognosis
Can transform into acute lymphoblastic leukaemia
Hyposplenism - causes
Splenectomy
Auto-infarction e.g., sickle cell disease
infiltration - metastatic malignancy
Under-function - coeliac disease
Neutrophilia - causes
Primary
- Myeloproliferative disorder e.g., chronic myeloid leukaemia
Secondary
- Bacterial infection
- Inflammatory conditions
- Burns
- Cigarette smoking
- Steroids
- G-CSF
- Solid tumour
Lymphocytosis - causes
Viral infection e.g., EBV
Hyposplenism
TB
Brucellosis
Chronic lymphocytic leukaemia (CLL)
Lymphoma with ‘spill over’
Eosinophilia - causes
Allergic reactions
Vasculitis
Drus
Worm infestations
Cancer (especially solid tumours and lymphoma)
High grade lymphomas - characteristics
- Short history
- Grows quickly
- Patiently usually symptomatic
- Treatment always required immediately
- Potentially curable
- Treatment intensive chemotherapy
- Once chance to cure (or maybe two)
Low grade lymphomas - characteristics
- Often longer or ‘no’ history
- Grows slowly
- Patients often asymptomatic
- Treatment often not required (watch and wait)
- A lifelong illness
- Treatment generally less intensive chemotherapy
- Can usually treat again and again…
Lymphomas - clinical features
Hodgkin lymphoma - epidemiology
Males > females
Most common in young adults and over 60s
Hodgkin lymphoma - histological classification
Characterised by the presence of reed-sterner cells
Hodgkin lymphoma - types
- Classical
- Nodular sclerosis
- Mixed cellularity
- Lymphocytic-rich
- Lymphocytic-deplete - Nodular lymphocyte-predominant
Hodgkin lymphoma - clinical features
Lymphadenopathy - painless, alcohol may precipitate pain
‘B’ symptoms - fever, night sweats and weight loss (unexplained, > 10% in 6 months)
Mediastinal mass
Pruritus
Splenomegaly/hepatosplenomegaly
Malaise
Fatigue
Extra nodal disease - lung, CNS, skin and bone involvement
Hodgkin lymphoma - investigations
Bloods - FBC - U&eS, Bone profile, LDH, Uric acid, ESR
Imaging
- CXR
- PET CT: used in staging of disease
- CT neck, chest, abdomen and pelvis
- MRI
Additional
- Lumbar puncture and CSF analysis: in those with suspected CNS disease
- Echocardiogram
- Pulmonary function tests
- Bone marrow biopsy
Hodgkin lymphoma - laboratory features
- Anaemia (normochromic, normocytic; AIHA can occur)
- Leucocytosis
- Raised ESR
- Raised LDL
- Abnormal LFTs
Hodgkin lymphoma - staging used
Ann Arbour staging
Describe Ann Arbor staging
Stage I - single lymph node region
Stage 2 - two or more lymph node regions on the same side of the diaphragm
Stage 3 - two or more lymph node region above and below the diaphragm
Stage 4 - widespread disease; multiple organs with out with lymph node involvement
A: absence of B symptoms
B: fever, nights sweats and weight loss
Hodgkin lymphoma - management
Chemotherapy
Non-hodgekin lymphoma - histological classification
Characterised by no reed-sternberg cells
Non-hodgkin lymphoma - presentation
Lymphadenopathy
‘B’ symptoms - fever, night sweats and weight loss (unexplained, > 10% in 6 months)
Pruritus
Splenomegaly
Hepatomegaly
Non-hodgkin lymphoma - investigations
Bloods – FBC, U&Es, LFTs, Bone profile, LDH, Uric acid, ESR,
Imaging
- CXR
- PET CT: Used in the staging of disease
- CT neck, chest abdomen and pelvis
- MRI brain
- Bone scan
Additional
- Lumbar puncture and CSF analysis: in those with suspected CNS disease
- Bone marrow aspirate and biopsy
Non-hodgkin lymphoma - investigations - laboratory features
Anaemia or pancytopenia
Peripheral blood lymphocytosis
Paraprotein (especially in lymphoplasmacytic lymphoma) or hypogammaglobinaemia
Serum LDH raised in more aggressive forms
Raised serum B2-microglobulin
Non-hodgkin lymphoma - staging used
Ann arbour staging
Non-hodgekin lymphoma - high-grade lymphomas examples
Diffuse large b-cell lymphoma
Burkitt lymphoma
Burkitt’s Lymphoma - appearance on biopsy
‘Starry’ appearance
What type of non-hodgekin lymphoma is associated with Helicobacte Pylorir?
Gastric MALT (mucosa-associated lymphoma tissue
What types of non-hodgekin lymphoma is associated with EBVr?
Burkitt’s lymphoma
(AIDS-related CNS lymphoma)
What types of Non-hodgekin lymphoma is associated with hepatitis C
Large B-cell lymphoma
(Splenic marginal zone lymphoma)
Non-hodgekin lymphoma - management
Chemotherapy
